12-21862088-T-C

Variant names:

• chr12-21862088-T-C
• rs704191
• NM_020297.4:c.2339+865A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020297.4(ABCC9):​c.2339+865A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.605 in 151,886 control chromosomes in the GnomAD database, including 28,315 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.60 (28315 hom., cov: 30)
• Consequence: ABCC9 NM_020297.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0370
• Publications: 11 publications found

Genes affected

ABCC9 (HGNC:60): (ATP binding cassette subfamily C member 9) The protein encoded by this gene is a member of the superfamily of ATP-binding cassette (ABC) transporters. ABC proteins transport various molecules across extra- and intra-cellular membranes. ABC genes are divided into seven distinct subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, White). This protein is a member of the MRP subfamily which is involved in multi-drug resistance. This protein is thought to form ATP-sensitive potassium channels in cardiac, skeletal, and vascular and non-vascular smooth muscle. Protein structure suggests a role as the drug-binding channel-modulating subunit of the extra-pancreatic ATP-sensitive potassium channels. Mutations in this gene are associated with cardiomyopathy dilated type 1O. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2011]

ABCC9 Gene-Disease associations (from GenCC):

• hypertrichotic osteochondrodysplasia Cantu type

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, G2P, Orphanet, Labcorp Genetics (formerly Invitae), ClinGen
• dilated cardiomyopathy 1O

  Inheritance: AD Classification: STRONG, MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Illumina, Ambry Genetics
• intellectual disability and myopathy syndrome

  Inheritance: AR Classification: MODERATE, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• acromegaloid facial appearance syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• familial isolated dilated cardiomyopathy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• hypertrichosis-acromegaloid facial appearance syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• Brugada syndrome

  Inheritance: AD Classification: LIMITED, NO_KNOWN Submitted by: ClinGen, Genomics England PanelApp
• dilated cardiomyopathy

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen
• atrial fibrillation, familial, 12

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ENSG00000257022 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.699 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020297.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCC9	NM_020297.4	MANE Select	c.2339+865A>G		intron	N/A	NP_064693.2	O60706-2
	ABCC9	NM_001377273.1		c.2339+865A>G		intron	N/A	NP_001364202.1	O60706-2
	ABCC9	NM_005691.4		c.2339+865A>G		intron	N/A	NP_005682.2	O60706-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCC9	ENST00000261200.9	TSL:5 MANE Select	c.2339+865A>G		intron	N/A	ENSP00000261200.4	O60706-2
	ABCC9	ENST00000261201.10	TSL:5	c.2339+865A>G		intron	N/A	ENSP00000261201.4	O60706-1
	ABCC9	ENST00000879186.1		c.2339+865A>G		intron	N/A	ENSP00000549245.1

Frequencies

GnomAD3 genomes AF: 0.605 AC: 91813 AN: 151768 Hom.: 28305 Cov.: 30

Gnomad AFR AF: 0.707

Gnomad AMI AF: 0.673

Gnomad AMR AF: 0.662

Gnomad ASJ AF: 0.531

Gnomad EAS AF: 0.699

Gnomad SAS AF: 0.523

Gnomad FIN AF: 0.573

Gnomad MID AF: 0.516

Gnomad NFE AF: 0.538

Gnomad OTH AF: 0.595

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.605 AC: 91864 AN: 151886 Hom.: 28315 Cov.: 30 AF XY: 0.607 AC XY: 45024 AN XY: 74210

African (AFR) AF: 0.706 AC: 29237 AN: 41412

American (AMR) AF: 0.662 AC: 10100 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.531 AC: 1841 AN: 3468

East Asian (EAS) AF: 0.699 AC: 3611 AN: 5166

South Asian (SAS) AF: 0.522 AC: 2512 AN: 4812

European-Finnish (FIN) AF: 0.573 AC: 6035 AN: 10540

Middle Eastern (MID) AF: 0.503 AC: 147 AN: 292

European-Non Finnish (NFE) AF: 0.538 AC: 36512 AN: 67924

Other (OTH) AF: 0.595 AC: 1255 AN: 2108

Alfa AF: 0.561 Hom.: 42932

Bravo AF: 0.617

Asia WGS AF: 0.601 AC: 2088 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.6
DANN	Benign	0.70
PhyloP100		0.037
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs704191; hg19: chr12-22015022;